Another way: each transformation gets its own substitution. This depends on discriminating between different types of  \d+ groups by their preceding patterns. Needs Perl version 5.10+ for the  \K regex operator; can be re-written to avoid using  \K (i.e., for pre-5.10) if needed.

c:\@Work\Perl\monks>perl -wMstrict -le
"use 5.010;
 ;;
 my $str = 'hello nr34,nr56,78, 98 , hi, 76';
 print qq{'$str'};
 ;;
 $str =~ s{ (nr\d+) }{calc($1);}xmsg;
 $str =~ s{ , \s* \K (\d+) }{ $1 * 4 }xmsge;
 print qq{'$str'};
"
'hello nr34,nr56,78, 98 , hi, 76'
'hello calc(nr34);,calc(nr56);,312, 392 , hi, 304'
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