The ectoparasitic mite, Varroa destructor, vectors lethal honeybee viruses, in particular Deformed wing virus (DWV) and is unarguably the leading cause of honeybee (Apis mellifera) colony mortality world-wide causing critical economic and ecological. Since the introduction of the mite in the 1970s and 1980s, wild honeybees in Europe and North America have been nearly completely eradicated and managed honeybees only survive through mite control treatment, or otherwise die within 1-2 years. These treatments consequences for pollination-dependent crop production and wild plant remove the selective pressure necessary to establish a stable host-parasite relationship, which hampers the evolution of resistance and obstructs fundamental research on natural selection host‒parasite coevolution in this new host‒parasite system, which is now only possible in a few small honeybee populations surviving long-term (>20 years) without varroa control in Sweden, France and Norway. These rare and valuable naturally selected populations offer unique insight into the natural adaptive capacity of honeybees, yet little is understood about their mechanisms of resistance or tolerance to varroa mites and the viruses they vector. Having exclusive access to these populations, the BEE NATURAL project sets out to comprehensively describe their host resistant and tolerant phenotypes towards both mites and viruses, using a variety of innovative experimental designs, in order to deeper our fundamental understanding of host-parasite interactions. Genomic regions or target genes associated with resistant and tolerant traits will be identified using Next Generation Sequencing (NGS) technologies such as RNA-seq and whole genome sequencing (WGS), providing valuable information that can be applied towards developing marker-assisted selection: a powerful new approach for disease resistant breeding that can facilitate major advances in breeding efforts and genetic stock improvement.