Lung ischemia–reperfusion injury (IRI), a significant factor contributing to early mortality following lung transplantation (LTx), is driven by molecular mechanisms that are not yet fully understood. In this study, we elucidate a crucial signaling pathway initiated by extracellular histones (ex-His), which connects mitochondrial damage to inflammatory cell death. Through the use of a murine model of lung IRI and in vitro exper...