This study aims to bridge the gap between the physiological response of Polar cod, Boreogadus saida, to ocean acidification and global warming, and the underlying molecular mechanisms. In this comprehensive project, a variety of physiological parameters (e.g.: growth and exercise) were investigated in response to ocean warming and acidification. The fish were long-term acclimated to three different CO2 concentrations: 390 ppm, a moderate increase (780 ppm), and high PCO2 levels corresponding to the business-as-usual greenhouse gas emission scenario (RCP8.5, 1170 ppm). Each CO2 treatment was combined with four temperatures, 0, 3, 6, 8°C to simulate different warming scenarios. In this study, we focused on the transcriptomic profiles from liver of these incubated and physiologically tested fish to identify critical molecular mechanisms underlying the previous reported physiological responses. Generally, we did not detect signs of a classical stress response, even at the highest temperature after four months of exposure. Consistent with previous observations, the molecular responses to ocean acidification were minor compared to temperature, but an interaction between both factors existed at least for some metabolic processes. Gene ontology analysis revealed a strong response in lipid-, carbohydrate- and protein metabolism. With increasing temperature, we observed a shift away from lipid metabolism, while carbohydrate metabolic pathways remained stable. Although we found Polar cod to be highly resilient to ocean acidification, temperature will remain a critical parameter for this valuable Arctic keystone species and the question remains whether adaptation mechanisms can be implemented in its natural habitat, especially when food supply is limited.