The livebearers platyfish and swordtails partially regenerate their hearts with persistent scarring

Heart regeneration varies among vertebrates, with zebrafish serving as a reference species for efficient cardiac restoration. How this capacity diversified among teleosts is an emerging question, given the recent identification of non-regenerative cardiac repair in medaka and cavefish. Here, we investigate heart restorative capacity following cryoinjury in two livebearers, platyfish and swordtails ( Xiphophorus species), belonging to the Poe-ciliidae family. We demonstrate that their hearts lack the vascularized compact myocardium, which is a ventricular layer implicated in the restorative response in zebrafish. After cryoinjury, both poeciliids failed to rapidly deposit fibrotic tissue that normally reinforces the damaged site. This deficiency led to striking wound protrusion reminiscent of pseudoaneurysm after myocardial infarction in humans. Although the remaining myocardium initially increased cell proliferation, subsequently deposited collagenous scar tissue permanently sealed the interrupted ventricle, preventing complete regeneration. Transcriptomic analysis revealed several divergently regulated pathways between cryoinjured hearts of zebrafish and platyfish, particularly in immune response regulation. This was validated by delayed leukocyte infiltration and prolonged inflammation in platyfish, compared to the rapid, resolved inflammatory response in zebrafish. Our findings demonstrate that Xiphophorus species have evolved hearts with compromised regenerative capacity, characterized by pseudoaneurysm-like protrusion and permanent scarring. These results reveal that evolutionary traits of phylogenetic lineages can fundamentally modulate regenerative competence among teleosts, with important implications for understanding the mechanistic basis of cardiac repair.