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Abstract The drylands vesper mouse (Calomys musculinus)is the primary host forJunin mammarenavirus(JUNV), the etiological agent of Argentine hemorrhagic fever in humans. We assessed the potential distribution ofC. musculinusand identified disease transmission hotspots under current climatic conditions and projected future scenarios, including severe (Representative Concentration Pathway 8.5) and intermediate (Representative Concentration Pathway 4.5) climate change scenarios in 2050 and 2070. Utilizing tree-based machine learning algorithms, we modeledC. musculinusdistribution by incorporating bioclimatic and landscape predictors. The model showed strong performance, achievingF-scores between 80.22 and 83.09%. Key predictors indicated thatC. musculinusprefers warm temperatures, moderate annual precipitation, low precipitation variability, and low pasture coverage. Under the severe climate change scenario, suitable areas for the rodent and hotspots for potential disease decreased. The intermediate scenario showed an expansion inC. musculinusdistribution alongside increased potential hotspot zones. Despite the complexity of ecological systems and the limitations of the model, our findings offer a framework for preventive measures and ecological studies in regions prone to the expansion ofC. musculinusand in hotspots for disease transmission driven by climate change.