We utilized peptidomics technology to identify natural Histone-derived-peptides in M. coruscus serum. Using peptidomic technique, a total of 2,335 peptides was identified from the four groups of mussel serum, including the serum sample of the control mussel group and other three mussel groups with microbe-injection. Of which, 712 peptides with -10lgP≥20 and FDR <0.01were matched to 92 histones by searching against M. coruscus histone database. Using peptidomic technique, a total of 2,335 peptides was identified from the four groups of mussel serum, including the serum sample of the control mussel group and other three mussel groups with microbe-injection. Of which, 712 peptides with -10lgP≥20 and FDR <0.01were matched to 92 histones by searching against M. coruscus histone database.