BackgroundThe drylands vesper mouse (Calomys musculinus)is the principal host forJunin mammarenavirus(JUNV), which causes Argentine Hemorrhagic Fever (AHF) in humans. In our study, we aimed to assess the probable range ofC. musculinusand to identify hotspots for potential disease transmission to humans under current and future climate change scenarios.Methodology/Principal FindingsWe used tree-based machine learning (ML) classification algorithms to generate and projectC. musculinushabitat suitability under two climate change scenarios for the years 2050 and 2070 using bioclimatic and landscape related predictors. Evaluation of the models showed high accuracy, with AUCROCranging from 86.81-89.84%. The analysis of the importance and influence of different variables indicated that the rodent prefers warm temperatures, moderate annual precipitation, low precipitation variability, and low pasture coverage. While a severe climate change scenario (Representative Concentration Pathway 8.5) suggests a reduction in suitable areas for JUNV reservoir and a decrease in hotspots for potential disease transmission, an intermediate scenario (Representative Concentration Pathway 4.5) displays expansion in areas forC. musculinusdistribution alongside increased potential hotspot zones.Conclusions/SignificanceWhile acknowledging the complexity of ecological systems and the limitations of the species distribution models, our findings offer a framework for developing preventive measures and conducting ecological studies in regions prone toC. musculinusexpansion and hotspots for potential disease transmission driven by climate change. Preventive interventions will need to be adapted to targetC. musculinuschanging spatial dynamics.Author SummaryClimate change might modify where animals live, including those that carry diseases than can spread to humans. This study focused on how climate change might affect the drylands vesper mouse (Calomys musculinus). This rodent carries the Junin virus, which causes Argentine Hemorrhagic Fever, a dangerous disease if left untreated. We used species distribution models to predict how this rodent’s range might change by 2050 and 2070 under an intermediate and severe climate change scenario.We found that a temperature rise of 1.1°C to 2.6°C (intermediate change scenario) could allow the rodent to move into new areas, potentially increasing disease transmission to humans. These new areas might have warm temperatures, moderate rainfall, and low grass cover, as we found thatC. musculinusprefers those climate and landscape conditions.Knowing the rodent’s potential distribution and preferred habitat enables preparedness and monitoring for early warning systems. By establishing monitor systems and online platforms featuring species distribution models and predictions, we can facilitate communication and resource sharing among researchers, policymakers, healthcare professionals and the public. These tools will help protect public health as climate change continues to bring new challenges.