13 Pág. Global warming and the changes in environmental conditions such as temperature and salinity may affect the health of marine species. However, the underlying mechanisms remain poorly characterized. The objectives of the present study were to examine the liver transcriptome and proteome of the marine species, hybrid grouper (E. fuscoguttatus ♀ × E. lanceolatus ♂), to assess which physiological pathways are modulated by exposure to climate change-related stressors, how the responses vary with exposure duration, and whether they represent adaptive or maladaptive changes. To answer these questions, the hybrid grouper was subjected to single stressors (elevated temperatures, reduced salinity) or stressor combinations for 3 or 14 days. As endpoints, we examined changes in body and organ growth, liver histopathology, lipid accumulation, and alterations of the liver transcriptome and proteome. The results demonstrated that the elevated temperature resulted in reduced body weight and a reduced liver-somatic index after a 14-day exposure. The spleen-somatic index was significantly decreased compared to controls after 3-day treatment. At the transcriptomic level, the pathways with the greatest numbers of differentially expressed genes at day 3 of exposure were immune-related in all treatment groups. After 14 days of exposure, the transcriptomic and proteomic analyses showed that metabolic and protective processes became activated. The increased lipid droplet accumulation in the hepatocytes is corroborated by the transcriptomic/proteomic findings which show alterations in the pathways of lipid metabolism and fatty acid oxidation. While these changes may represent adaptive responses, the increase of hepatic lipid accumulation despite an overall loss of liver and body weight may represent a maladaptive process. Overall, the physiological responses of the hybrid grouper showed a clear time dependency, and they were partly stressor-specific, with the low salinity treatment separating from the treatments with elevated temperature. When both stressors were combined, the temperature effect dominated the salinity effect. This work was sponsored by the National Key Research and Development Program of China (No. 2017YFA0604902 ) and the National Natural Science Foundation of China (No. 41977211 ). The authors would like to thank Dr. Hongjian Tan for his discussion on future climate change. Peer reviewed