BrowserUk’s solution is cleaner; but, in the spirit of TMTOWTDI, here’s an approach using the qr// operator:

#! perl
use strict;
use warnings;

my @all_patterns =
(
    [ qr{#.*},    ''    ],      # 0. Comments
    [ qr{^\s+},   ''    ],      # 1. Initial whitespace
    [ qr{\s+$},   ''    ],      # 2. Final whitespace
    [ qr{^Total}, 'Sum' ],      # 3. Initial "Total" --> "Sum"
    [ qr{^,},     ''    ],      # 4. Initial comma
);

while (<DATA>)
{
    my $string = apply_patterns($_, 0, 2, 3, 4);
    print "$string\n" if $string;
}

sub apply_patterns
{
    my ($string, @indices) = @_;

    chomp $string;
    $string =~ s{$all_patterns[$_]->[0]}
                {$all_patterns[$_]->[1]}g for @indices;
    return $string;
}

__DATA__
   First line # comment
Total: Second line   
# Third line
,Fourth line
[download]

Output:

23:23 >perl 701_SoPW.pl
   First line
Sum: Second line
Fourth line

23:23 >
[download]

Note: Depending on the nature of the filters, you may need to give careful attention to the order in which they are applied.

Hope that helps,