Stability Analysis of a Nonautonomous Diffusive Predator–Prey Model with Disease in the Prey and Beddington–DeAngelis Functional Response

Based on existing models, this paper incorporates some key ecological factors, thereby obtaining a class of eco-epidemiological models that can more objectively reflect natural phenomena. This model simultaneously integrates disease dynamics within the prey population and the Beddington–DeAngelis functional response, thus achieving an organic combination of ecological dynamics, epidemic transmission, and spatial movement under time-varying environmental conditions. The proposed framework significantly enhances ecological realism by simultaneously accounting for spatial dispersal, predator–prey interactions, disease transmission within prey species, and seasonal or temporal variations, providing a comprehensive mathematical tool for analyzing complex eco-epidemiological systems. The theoretical results obtained from this study can be summarized as follows: Firstly, the existence and uniqueness of globally positive solutions for any positive initial data are rigorously established, ensuring the well-posedness and biological feasibility of the model over extended temporal scales. Secondly, analytically tractable sufficient conditions for uniform population persistence are derived, which elucidate the mechanisms of species coexistence and biodiversity preservation even under sustained epidemiological pressure. Thirdly, by employing innovative applications of differential inequalities and fixed point theory, the existence and uniqueness of a positive spatially homogeneous periodic solution in the presence of time-periodic coefficients are conclusively demonstrated, capturing essential rhythmicities inherent in natural systems. Fourthly, through a sophisticated combination of the upper and lower solution method for parabolic partial differential equations and Lyapunov stability theory, the global asymptotic stability of this periodic solution is rigorously established, offering a powerful analytical guarantee for long-term predictive modeling. Beyond theoretical contributions, these research findings provide actionable insights and quantitative analytical tools to tackle pressing ecological and public health challenges. They facilitate the prediction of thresholds for maintaining ecosystem stability using real-world data, enable the analysis and assessment of disease persistence in spatially structured environments, and offer robust theoretical support for the planning and design of wildlife management and conservation strategies. The derived criteria support evidence-based decision-making in areas such as controlling zoonotic disease outbreaks, maintaining ecosystem stability, and mitigating anthropogenic impacts on ecological communities. A representative numerical case study has been integrated into the analysis to verify all of the theoretical findings. In doing so, it effectively highlights the model’s substantial theoretical value in informing policy-making and advancing sustainable ecosystem management practices.