bioRxiv2025
Highly pathogenic avian influenza (HPAI) has become a critical threat to wildlife, shifting from a seasonal epizootic to a persistent, year-round panzootic with global consequences. Here, we summarize the origin, evolutionary mechanisms, and expanding host range of the current H5N1 virus (clade 2.3.4.4b) and assess its impact on wildlife. Over the past five years, HPAI has caused the deaths of millions of wild birds, causing dramatic population declines in several seabird species. However, comprehensive quantitative mortality data remain scarce, as existing records are often anecdotal, focus on localized mass die-offs, and thus represent only a fraction of the true magnitude of mortality. This gap in data limits the ability to predict outbreak dynamics and mitigate long-term consequences. Using the Northwestern European Sandwich Tern (Thalasseus sandvicensis) population as a case study, we demonstrate the value of integrating mortality data with ecological, serological and genetic data before, during and after an outbreak. This approach uncovered age-specific vulnerability, selective mortality, and population immunological responses. In addition, insights gained with respect to the role of breeding density, carcass removal, and host adaptation in modulating outbreak dynamics are likely to be generalizable across seabird species. The absence of a centralized and standardized wildlife mortality monitoring framework, on the other hand, remains a major barrier to effective outbreak forecasting and conservation planning. We argue that integrating field-based mortality data, population monitoring, serological assays, and genetic analyses within a One Health framework is essential to enable early detection, targeted mitigation, and robust evaluation of outbreak impacts. Without a proactive and data-driven approach to conservation, HPAI will continue to threaten global wildlife populations, with cascading ecological, economic and public health consequences.