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 summarise 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 5 years, HPAI has caused the deaths of millions of wild birds, causing dramatic population declines in several seabird species. Mortality records, however, are often anecdotal, focus on localised mass die-offs, and thus represent only a fraction of the true mortality. This lack of quantitative 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, and provided insights into how breeding density, carcass removal, and host adaptation modulate outbreak dynamics. The absence of a centralised and standardised wildlife mortality monitoring framework, on the other hand, remains a major barrier to effective outbreak forecasting and conservation planning. We argue that integrating population and mortality 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, and caution that 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.