Globally, large mammals are increasingly faced with anthropogenic disturbances threatening the sustainability of the ecosystem services derived from them. Changes in land use cover are also a major function of anthropogenic forces which has a considerable potential to offset large mammal populations. With the need to conserve these biological resources, the impact of human activities and land-use changes on the diversity and distribution of large mammals was assessed in Nimule National Park using a total of 34 transects distributed across the heavily disturbed (buffer) and relatively undisturbed park area (inside the park). Shannon Wiener Index was used to measure the diversity of large mammals and polynomial multiple regressions was used to evaluate the impact of human activities on large mammals’ species. Supervised image classification algorithms based on maximum likelihood were used to detect land-use changes from the Landsat satellite imagery for the years 1996, 2006 and 2016. The diversity of large mammals was not significantly different between the buffer and the interior of the park. However, larger mammals’ distribution was significantly different among different habitat types. The most prevalent human activities observed in the study area were livestock grazing, firewood collection, and poaching. Human activities did not have a significant impact on the abundance of large mammals. The land use/cover change analysis results revealed that between the periods of 1996 to 2006, there was a decrease in the built-up area (3.7%), farmland (2.8 %), and open woodland (63.7%). These changes could be attributed to the displacement of local communities because of the civil war during that period. For the period 2006 to 2016, there was an observed increase in a built-up area (3.1%) and open woodland (49.7%) and a decrease in grassland (29.5%), farmland (0.7%), and open forest (21.7%) cover. The results from remote sensing indicated that there were significant changes in some land uses and land cover classes. The study recommends a detailed survey to be carried out on the population status of all mammals’ species in the park and the impact of human activities on their behaviours well as monitoring their habitats through satellite images every ten years.

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