Intellectual Merit Coral diseases have increased significantly throughout the past 30 years. Unhealthy coral reefs cannot support fish and other life that make the reef a vibrant and diverse ecosystem. Coral reefs in the Caribbean have experienced population collapses due to outbreaks of disease. One disease in particular, Stoney Coral Tissue Loss Disease is a new fast spreading and lethal disease first reported in Florida in 2014. SCTLD affects over 30 species of corals including the iconic brain and pillar corals. Since its discovery in Florida, the disease has spread to Caribbean and was first detected in US Virgin Islands in 2019. In this study we conducted experiments to understand how this disease affects immune traits and immune responses of five coral species. It also examines how changing the species composition of a coral community affects the spread and impact of the disease. We therefore quantified coral susceptibility to disease and examined coral immune mechanisms that may drive disease outcomes. In response to exposure to Stoney Coral Tissue Loss Disease the five species of corals had one of two treatment outcomes, exposed to disease and not infected or infected with a visible lesion, leading to a gradient of susceptible, moderately susceptible, and tolerant. We leveraged this range of coral responses to SCTLD exposure to determine the patterns of gene expression associated with SCTLD resistance or susceptibility. The gene expression profiles of coral hosts and their endosymbionts were examined independently by bioinformatically separating the RNA-seq reads prior to analyses. We show that SCTLD exposure induces significant transcriptional changes in both the coral animal and their algal symbionts, altering normal host-symbiont interactions. We identify orthologous coral genes exhibiting lineage-specific differences in constitutive expression that correlate to disease susceptibility, as well as those that are significantly differentially expressed in all coral species in response to SCTLD infection. We have several significant findings: First, we find that SCTLD infection induces genes involved in antiviral immunity, symbiont maintenance, starvation, and apoptosis in all five coral species. Second, species-specific differences in SCTLD susceptibility involve increased vesicular trafficking and decreased signal transduction. Third, the intracellular algal symbiont, rather than the coral animal, are the first to exhibit gene expression shifts in response to SCTLD exposure. Taken together our data show that SCTLD disrupts normal host-symbiont interactions, leading to starvation of the coral host and subsequent in situ degradation of intracellular Symbiodiniaceae. We find that SCTLD-exposure induces initial shifts in endosymbiont gene expression, followed by expression of coral genes involved in immunity, starvation, and apoptosis. Overall, our results indicate that SCTLD infection induces in situ degradation of dysfunctional endosymbionts across species and that the severity of disease is strongly influenced by the identity of the symbiont genera within the coral. Broader Impacts This project supported students at University of Texas, Arlington (Hispanic-serving Institution). Over the funding period, 2 graduate students were directly funded and trained on the award, another 2 benefited indirectly from assisting with field work, and spin-off projects resulting from the large amount of data collected from this award. This award also supported the training in marketable skills such as RNA and DNA extractions, bioinformatic tools and statistical modelling, of 2 undergraduate students who were mentored by graduate students in the lab. Public outreach was limited due to COVID shutdowns, but we were able to host one booth in April 2022 at the large EarthX expo in Dallas. All Mydlarz lab students all took part in developing activities and interacting with the public at these events, where we estimate engagement with about 1800 people. PI Mydlarz also led several workshops targeting women in science and the concept of sponsorship vs mentorship. To date this award has led to the publication of 5 papers, with one manuscript currently in review and multiple others in a stage of writing and/or development. There were approximately fifteen presentations by graduate and undergraduate students at various conferences. PI Mydlarz co-led a special issue of Frontiers of Immunology, a session at the 14th International Coral Reef Symposium all related to the topic and data from this award. Last Modified: 09/12/2022 Submitted by: Laura D Mydlarz