Marine heatwaves are increasing in frequency and intensity and ocean acidification is shifting ocean chemistry, with potentially catastrophic consequences for marine taxa and ecosystems such as coral reefs. This project focused on environmentally realistic, extended heatwave and recovery time series in a multi-stressor experimental framework to provide biological understanding and enhanced predictive capacity for the performance of corals under climate change. Specifically the goal was to determine the contributions of the multiple symbiotic partners through mechanisms that provide acclimatory responses to such environmental stressors. The project provided training and professional advancement for undergraduate and graduate students, technicians, and postdoctoral scholars in the areas of ecology, physiology, molecular biology, coding, bioinformatics, and statistics, as well as oral and written presentations of the results. These skills equipped the trainees to be globally engaged scientists prepared to tackle emerging marine science challenges. This project began on the heels of the 2014-2016 3rd mass bleaching event declared by the National Oceanic and Atmospheric Administration that had devastating consequences for the ecology of reefs globally, and particularly for the USA in Hawaiʻi. We exposed two common reef-building corals in Hawaiʻi, Montipora capitata and Pocillopora acuta, to a two-month period of high temperature and high pCO2 conditions (29.5 °C, ~1100 ppm) or ambient conditions (27.5 °C, ~500 ppm) in a factorial design, followed by two months of return to ambient conditions. In response to high temperature, but not high pCO2, the multivariate physiology of both species shifted through time, driven by decreases in respiration rates and endosymbiont density. P. acuta exhibited more significantly altered physiology, and substantially higher bleaching and mortality than M. capitata. Additionally, we exposed these same species (and the anemone Exaiptasia pallida) to increased temperature of 2.7° to 3.2°C above ambient temperature for 5 weeks. Quantification of polar metabolites, or small molecules that indicate metabolic state, identified a set of four dipeptides that were diagnostic of thermal stress. In both our short term and extended heatwave and climate change stressor scenarios, our results indicated a species-specific negative impacts on corals that were driven by inherent differences in both host and symbiont physiology. Notably, the corals that survived these projected conditions exhibited lasting physiological legacies that are likely to influence the holobiontʻs future stress response. To identify molecular mechanisms underlying stress response in corals we: 1) sequenced the genomes and DNA methylomes of four species of corals from Hawaiʻi as genetic and epigenetic (i.e., mechanisms enabling changes in gene expression without changes in DNA bases) resources; 2) sequenced the metabolomes, transcriptomes, DNA methylomes, and symbiotic communities of sensitive to resistant coral taxa; and 3) analyzed the multi-omic data sets with network level approaches to quantify connections between metabolites and genes and organismal phenotype. Collectively, our results reveal variation in symbiont communities, epigenetic states, and small molecular production, as well as key tissue characteristics such as biomass, protein, and cell density, drive coral responses in contrasting ways following exposure to environmental stress. Furthermore, our project provides for the public and the scientific community a wealth of open access data, code, and protocols through archival in BCO-DMO, Github repositories, Online lab notebooks, and NCBI SRA datasets. Last Modified: 01/29/2023 Submitted by: Hollie M Putnam