Anthropogenic CO2 emissions threaten marine ecosystems by increasing water temperature and acidification. Fish generally seem to be less sensitive to elevated CO2 concentrations due to their efficient ion regulatory capacities. As temperature affects all ion regulatory processes, an increased sensitivity to elevated CO2 levels at the edges of the thermal window can be postulated. In this study, we are acclimating Atlantic cod to a combined setup of elevated PCO2 (390, 1120 and 3000 µatm) and temperatures (10, 15 and 18 °C). In isolated, perfused gill arches we determine the fractional costs of ion regulation, protein and RNA synthesis in relation to the global energy budget after acclimation and under acute exposure by the application of specific inhibitors. Acute warming increased overall gill oxygen consumption rates and fractional costs of the processes investigated, the latter most obvious when combined with hypercapnia. Furthermore, apical Na+/H+ exchangers seem to be essential for the response towards acidification. In isolated gill cells we fluorometrically track the changes of intracellular pH in gill cells after acute exposure to acidification to quantify cellular ion regulative processes and performance. Additionally, ion transport proteins are going to be inhibited to quantify their involvement in the entire regulation process. For the characterisation of the ion regulatory transcriptome and proteome we combine genetic, immunohistological and functional approaches. So far, genes of essential transporters involved in ion regulation have been isolated, and the expression of relevant transporters (NBC1, AE1, H+-ATPase, Na+/K+-ATPase) and the capacity of the Na+/K+-ATPase were found seasonally and population specific regulated. Measuring a portfolio of haematological and immunological endpoints the hypothesis is tested whether increased energy expenditure e. g. for ion regulation at elevated CO2 levels will suppress the immunocompetence at the edges of the cods thermal window. Together, all data will be integrated into a mechanistic model to mathematically formulate ion regulative capacities and its limitations in response to predicted climate scenarios.