show Abstracthide AbstractSingle-cell RNA sequencing is revolutionizing the mapping of tissues in physiology and pathology. Whilst immune responses are emerging as key mediators of heart failure, no thorough immune mapping of the ailing heart has been performed so far. Here we examined, at single-cell level, the cardiac immune composition after transverse aortic constriction, the standard murine model of non-ischemic heart failure. We identified the presence of most major immune cell subpopulations in the myocardium of both healthy and cardiopathic mice. Despite the absence of infectious agents or an autoimmune trigger, the ailing heart, especially at late-stage disease, is characterized by an immune activation that is both drastic and far more wide-ranging in the immune cell types involved than previously thought. The molecular-level detail we uncover in the cells undergoing activation in response to cardiac stress may enable the identification of novel biomarkers and therapeutic targets for heart failure. Overall design: 4 experimental condtions, two time points