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Background: This study was part of a larger comprehensive project (BIOACID) addressing the physiological resilience of Polar cod, Boreogadus saida, to ocean acidification and global warming and aimed to unravel underlying molecular mechanisms of the observed physiological responses. Methods: Fish were acclimated long-term to three CO2 concentrations comprising control conditions (390 ppm) and two projected climate scenarios (780 ppm and 1170 ppm). Each CO2 treatment was combined with four temperatures: 0, 3, 6, and 8 °C. Here, we focused on the hepatic transcriptomic profiles from these previously physiologically characterized fish. Results: Generally, we did not detect signs of a classical stress response. Consistent with functional observations, warming induced much stronger molecular responses compared to elevated PCO2, but an interaction between both factors existed to some extent. Gene ontology analysis revealed a strong response in lipid, amino acid, and protein metabolism. With increasing temperature, we observed a shift away from lipid metabolism, while carbohydrate metabolic pathways remained stable. Conclusions: Although we found Polar cod to be quite resilient to ocean acidification, temperature will remain a critical parameter for this valuable Arctic keystone species, and the question remains as to whether the observed acclimation strategies can be implemented in its natural habitat, especially when food supply is limited.