Highly unsaturated fatty acids of the omega-3 series (HUFA) are major constituents of cell membranes, yet poorly synthesised de novo by consumers. Their production, mainly supported by aquatic microalgae, has been decreasing with global change. Understanding the consequences of such reductions is essential for ectotherm consumers, since temperature tightly regulates the HUFA content in cell membranes, maintaining their functionality. Integrating individual, tissue and molecular approaches, we examined the consequences of the combined effects of temperature and HUFA depletion on the key cardio-respiratory functions of the golden grey mullet, an ectotherm grazer of high ecological importance. For four months, fish were exposed to two contrasting HUFA diets (4.8% ecosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) on dry matter (DM) vs. 0.2% EPA+DHA on DM) at 12°C and 20°C. Ventricular force development coupled with gene expression profiles measured on cardiac muscle suggest that combining HUFA depletion with warmer temperatures leads to (1) a proliferation of sarcolemmal and SR Ca2+ channels and (2) a higher force-generating ability by increasing extracellular Ca2+ influx via sarcolemmal channels when the heart has to sustain excessive effort due to stress and/or exercise. At the individual scale, these responses were associated with a relatively greater aerobic scope, maximum metabolic rate and net cost of locomotion, suggesting the higher energy cost of this strategy. These impaired cardiac performances could have wider consequences on other physiological performances such as growth, reproduction or migration, all greatly depending on heart function.